Mycobacterium Tuberculosis

Snapshot

• A 33-year-old man presents to his primary care physician for a cough and generalized malaise. His symptoms are associated with 2 episodes of mild hemoptysis and night sweats. He denies any sick contacts or recent travels; however, he states he was released from prison 4 months ago. Physical examination is unremarkable. A chest radiograph is obtained, which demonstrates pulmonary infiltrates and cavitations in the upper lobe.

Introduction

• Classification
  • acid-fast, rod-shaped, obligate aerobic, intracellular bacteria 
• Epidemiology
  • risk factors
    • traveling to endemic areas (e.g., Angola and the Central African Republic)
    • close contact (e.g., prisons, nursing homes, homeless shelters, and hospitals)
    • immunocompromised (e.g., HIV, immunosuppressive medications, and diabetes)
• Transmission
  • airborne spread of droplet nuclei from patients with infectious tuberculosis (TB)
• Microbiology
  • acid-fast on Ziehl-Neelsen staining 
  • immune system itself causes damage
    • TB contains no endotoxins or exotoxins
  • cord factor 
    • inhibits leukocyte migration
    • causes characteristic serpentine growth pattern
    • induces TNF-α release
  • tuberculin
    • triggers cell-mediated immunity → caseation and granulomas
    • triggers delayed hypersensitivity reaction
    • a surface protein
  • sulfatides
    • prevent phagosome-lysosome fusion
• Pathogenesis
  • the infected person coughs up small droplets containing the bacteria that reaches the terminal alveoli of the uninfected person
    • alveolar macrophages are recruited, which eventually become infected, transporting the microbe to deeper tissues 
    • more alveolar macrophages are recruited, leading to granuloma formation 
      • granulomas are formed to “wall off” TB, where it lies dormant  
  • secondary TB occurs when the patient’s immune system is weakened (e.g., newly acquired HIV infection, being on immunosuppressant medications, malignancy, and poor nutrition)
    • macrophages’ ability to maintain their barrier decreases, facilitating possible dissemination 
• TB infection typically manifests in the apical/posterior segments of the lung due to its increased oxygen tension

Presentation

• TB can lead to pulmonary and extrapulmonary manifestations
  • lymph nodes (tuberculous lymphadenitis)
  • pleura
  • genitourinary
  • skeleton (can lead to Pott disease with spinal involvement)
  • meninges
  • gastrointestinal system
  • pericardium (tuberculous pericarditis)
• Symptoms
  • typically asymptomatic in primary TB
  • cough
  • hemoptysis
  • fever
  • night sweats
  • malaise
• Physical exam
  • weight loss
  • lymphadenopathy
  • dullness to percussion or decreased/absent breath sounds if there is a pleural effusion
• back pain in spinal TB (Pott disease)

Imaging

• Chest radiograph
  • indication
    • initial imaging study in the evaluation of TB
  • findings
    • middle or lower lung infiltrate (suggestive of primary infection)
    • upper lobe infiltrate (suggestive of latent TB reactivation)
      • apices have higher oxygen tension and reduced perfusion/lymph clearance compared to the base 
    • cavitary lesions 
• Ghon complex (lobar or perihilar lymph node involvement) 

Studies

• Sputum acid-fast testing
  • demonstrates acid-fast bacilli
• Real-time nucleic acid amplification
  • rapidly confirms TB and is considered the first-line diagnostic study
• Tuberculin skin test (TST)
  • most widely used to screen for latent TB infection
  • a delayed-type hypersensitivity reaction against purified protein derivative (PPD) is induced
    • the size of the induration is assessed after 48-72 hours
    • note, patients who received the Bacille Calmette-Guerin (BCG) vaccination will have false positive results
    • a false negative result can be seen in immunocompromised patients
  • interpretation (positive results)
    • ≥ 15 mm in patients with no risk factors
    • ≥ 10 mm in patients with risk factors (e.g., healthcare worker, traveling to endemic areas, and being in prison)
    • ≥ 5 mm in immunocompromised patients (e.g., HIV, on immunosuppressants, and organ transplant recipients)
    • positive tests require a chest radiograph
• Interferon-γ release assay
  • measures interferon levels released by the patient’s immune system in response to TB antigens
• the results are not affected by previous BCG vaccination

Differential

• Lung cancer
  • differentiating factor
• patients will not have positive TB studies

Treatment

• Medical
  • rifampin, isoniazid, pyrazinamide, and ethambutol therapy 
    • indication
      • first-line treatment for active pulmonary TB infection for 4 months
        • after 4 months, treatment involves isoniazid and rifampin
    • comments
      • isoniazid can cause peripheral neuropathy as well as sideroblastic anemia due to vitamin B6 deficiency, thus warranting pyridoxine in hopes to prevent this development from occurring  
        • can also cause hepatitis
      • ethambutol can cause optic neuropathy 
      • mutations in RNA polymerase lead to rifampin resistance 
  • isoniazid monotherapy
    • indication
• prophylactic treatment for latent primary TB after active TB has been excluded 

Complications

• Pott disease
• Miliary or disseminated TB
• Meningitis
• Pericarditis
• Lymphadenitis
• Adrenal insufficiency